Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2

Kondo, Shuji; Tang, Yixin; Scheef, Elizabeth A.; Sorenson, Christine M.

doi:10.1152/ajpcell.90633.2007

Cited by 23 publications

(33 citation statements)

References 48 publications

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“…7C. Previous studies from our laboratories indicated that optimal endothelial cell migration is essential for capillary morphogenesis in vitro (4,7,14,29). Next, we determined whether decreasing eNOS expression restored capillary morphogenesis.…”

Section: Akita/ϩ Kidney Endothelial Cells Demonstrated Similar Levelsmentioning

confidence: 98%

Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes

Grutzmacher

Park

Zhao

et al. 2013

American Journal of Physiology-Renal Physiology

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Diabetic nephropathy is the most common cause of end-stage renal disease and is a major risk factor for cardiovascular disease. In the United States, microvascular complications during diabetic nephropathy contribute to high morbidity and mortality rates. However, the cell-autonomous impact of diabetes on kidney endothelial cell function requires further investigation. Male Akita/+ [autosomal dominant mutation in the insulin II gene (Ins2)] mice reproducibly develop diabetes by 4 wk of age. Here, we examined the impact a short duration of diabetes had on kidney endothelial cell function. Kidney endothelial cells were prepared from nondiabetic and diabetic mice (4 wk of diabetes) to delineate the early changes in endothelial cell function. Kidney endothelial cells from Akita/+ mice following 4 wk of diabetes demonstrated aberrant expression of extracellular matrix proteins including decreased osteopontin and increased fibronectin expression which correlated with increased α5-integrin expression. These changes were associated with the attenuation of migration and capillary morphogenesis. Kidney endothelial cells from Akita/+ mice had decreased VEGF levels but increased levels of endothelial nitric oxide synthase(eNOS) and NO, suggesting uncoupling of VEGF-mediated NO production. Knocking down eNOS expression in Akita/+ kidney endothelial cells increased VEGF expression, endothelial cell migration, and capillary morphogenesis. Furthermore, attenuation of sprouting angiogenesis of aortas from Akita/+ mice with 8 wk of diabetes was restored in the presence of the antioxidant N-acetylcysteine. These studies demonstrate that aberrant endothelial cell function with a short duration of diabetes may set the stage for vascular dysfunction and rarefaction at later stages of diabetes.

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Section: Akita/ϩ Kidney Endothelial Cells Demonstrated Similar Levelsmentioning

confidence: 98%

Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes

Grutzmacher

Park

Zhao

et al. 2013

American Journal of Physiology-Renal Physiology

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“…32 Loss of BCL2 was reported to inhibit migration of retinal endothelial cells, while enhancing cell adhesion and the motility of ureteric bud cells. 33,34 The cell type and context specific basis as to why different type of cells display different effects or even paradoxical opposite effects are not clear. In addition, distinct BCL2 expression level profiles of different cell type may dampen the BCL2 effect or even reverse its functions.…”

Section: Bcl2 Enhances Actin Polymerizationmentioning

confidence: 99%

BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization

Zhang

Akiyama

et al. 2011

Cell Adhesion & Migration

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In addition to its well-defined role as an antagonist in apoptosis, we propose that BCL2 may act as an intracellular suppressor of cell motility and adhesion under certain conditions. Our evidence shows that, when overexpressed in both cancer and non-cancer cells, BCL2 can form a complex with actin and gelsolin that functions to decrease gelsolin-severing activity to increase actin polymerization and, thus, suppress cell adhesive processes. The linkage between increased BCL2 and increased actin polymerization on the one hand and suppression of cell adhesion, spreading and motility on the other hand, is a novel observation that may provide a plausible explanation for why BCL2 overexpression in some tumors is correlated with improved patient survival. In addition, we have identified conditions in vitro in which F-actin polymerization can be increased while cell motility is reduced. These findings underscore the possibility that BCL2 may be involved in modulating cytoskeleton reorganization and may provide an opportunity to explore signal transduction pathways important for cell adhesion and migration and to develop small molecule therapies for suppression of cancer metastasis.

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“…We next determined the rate of apoptosis in TSP1 ϩ/ϩ and TSP1 Ϫ/Ϫ PCs in the presence or absence of 5-fluorouracil (1 mM), as previously described (23). We observed no significant differences in the rates of apoptosis in these cells (TSP1 ϩ/ϩ PCs: 1.2 Ϯ 0.09% vs. TSP1 Ϫ/Ϫ PCs: 1.4 Ϯ 0.12%, n ϭ 5, P Ͼ 0.05).…”

Section: Isolation Of Mouse Retinal Pcsmentioning

confidence: 99%

Attenuation of proliferation and migration of retinal pericytes in the absence of thrombospondin-1

Scheef¹,

Sorenson²,

Sheibani³

2009

American Journal of Physiology-Cell Physiology

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Scheef EA, Sorenson CM, Sheibani N. Attenuation of proliferation and migration of retinal pericytes in the absence of thrombospondin-1. Am J Physiol Cell Physiol 296: C724 -C734, 2009. First published February 4, 2009 doi:10.1152/ajpcell.00409.2008.-Perivascular supporting cells, including vascular smooth muscle cells (VSMCs) and pericytes (PCs), provide instructive signals to adjacent endothelial cells helping to maintain vascular homeostasis. These signals are provided through direct contact and by the release of soluble factors by these cells. Thrombospondin (TSP)1 is a matricellular protein and an autocrine factor for VSMCs. TSP1 activity, along with that of PDGF, regulates VSMC proliferation and migration. However, the manner in which TSP1 and PDGF impact retinal PC function requires further investigation. In the present study, we describe, for the first time, the isolation and culture of retinal PCs from wild-type (TSP1 ϩ/ϩ ) and TSP1-deficient (TSP1 Ϫ/Ϫ ) immortomice. We showed that these cells express early and mature markers of PCs, including NG2, PDGF receptor-␤, and smooth muscle actin as well as desmin, calbindin, and mesenchymal stem cell markers. These cells were successfully passaged and maintained in culture for several months without significant loss of expression of these markers. TSP1 ϩ/ϩ PCs proliferated at a faster rate compared with TSP1PCs. In addition, TSP1 ϩ/ϩ PCs, like VSMCs, responded to PDGF-BB with enhanced migration and proliferation. In contrast, TSP1Ϫ/Ϫ PCs failed to respond to the promigratory and proliferative activity of PDGF-BB. This may be attributed, at least in part, to the limited interaction of PDGF-BB with TSP1 in null cells, which is essential for PDGF proliferative and migratory action. We observed no significant differences in the rates of apoptosis in these cells. TSP1Ϫ/Ϫ PCs were also less adherent, expressed increased levels of TSP2 and fibronectin, and had decreased amounts of N-cadherin and ␣ v␤3-integrin on their surface. Thus, TSP1 plays a significant role in retinal PC proliferation and migration impacting retinal vascular development and homeostasis. retinal vasculature; platelet-derived growth factor; platelet-derived growth factor receptor-␤; mesenchymal stem cells; perivascular cells; cell adhesion ANGIOGENESIS, the formation of new blood vessels from preexisting capillaries, is a complex and multistep process. Pathological growth of new blood vessels contributes to a large number of eye diseases, including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration (4, 6, 13). However, the molecular and cellular events that contribute to the initiation of angiogenic events require further delineation. Specific alterations in vascular cells, including endothelial cells (ECs) and perivascular support cells [vascular smooth muscle cells (VSMCs) and pericytes (PCs)], may play an important role in these processes.The mouse retinal vasculature develops postnatally, providing a unique opportunity to study all aspects of ...

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Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2

Abstract: Kondo S, Tang Y, Scheef EA, Sheibani N, Sorenson CM. Attenuation of retinal endothelial cell migration and capillary morphogenesis in the absence of bcl-2.

Cited by 23 publications

References 48 publications

Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes

Aberrant production of extracellular matrix proteins and dysfunction in kidney endothelial cells with a short duration of diabetes

BCL2 interaction with actin in vitro may inhibit cell motility by enhancing actin polymerization

Attenuation of proliferation and migration of retinal pericytes in the absence of thrombospondin-1

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